NTNG2

Summary

NTNG2 (netrin G2, HGNC:14288) is a protein-coding gene on chromosome 9q34.13, encoding Netrin-G2 (Q96CW9). Involved in controlling patterning and neuronal circuit formation at the laminar, cellular, subcellular and synaptic levels.

Predicted to be involved in axonogenesis; regulation of cell projection organization; and regulation of neuron migration. Predicted to be located in plasma membrane. Predicted to be active in Schaffer collateral - CA1 synapse; glutamatergic synapse; and presynaptic active zone membrane.

Source: NCBI Gene 84628 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with behavioral abnormalities, absent speech, and hypotonia (Strong, GenCC) — +3 more curated relationships
• GWAS associations: 14
• Clinical variants (ClinVar): 180 total — 2 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 75
• MANE Select transcript: NM_032536

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14288
Approved symbol	NTNG2
Name	netrin G2
Location	9q34.13
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1857, Lmnt2, NetrinG2
Ensembl gene	ENSG00000196358
Ensembl biotype	protein_coding
OMIM	618689
Entrez	84628

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 15 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000393229, ENST00000483055, ENST00000490694, ENST00000922385, ENST00000922386, ENST00000922387, ENST00000946488, ENST00000946489, ENST00000946490, ENST00000946491, ENST00000946492, ENST00000946493, ENST00000946494, ENST00000946495, ENST00000946496, ENST00000946497, ENST00000946498

RefSeq mRNA: 1 — MANE Select: NM_032536 NM_032536

CCDS: CCDS6946

Canonical transcript exons

ENST00000393229 — 8 exons

Exon	Start	End
ENSE00001376934	132230572	132230595
ENSE00001415743	132162058	132162239
ENSE00003237954	132166349	132167044
ENSE00003262507	132241876	132244526
ENSE00003274648	132197966	132198609
ENSE00003361829	132240910	132241044
ENSE00003387259	132239104	132239271
ENSE00003396382	132226849	132227021

Expression profiles

Bgee: expression breadth ubiquitous, 173 present calls, max score 90.34.

FANTOM5 (CAGE): breadth broad, TPM avg 0.7606 / max 77.8307, expressed in 392 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
99135	3.3851	835
4324	0.7606	392
4322	0.6288	248
99131	0.5116	68
99134	0.4006	166
201600	0.2545	145
99133	0.1222	44
99136	0.1197	17
4323	0.0949	38
99137	0.0688	22

Top tissues by expression

243 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	90.34	silver quality
monocyte	CL:0000576	87.59	gold quality
leukocyte	CL:0000738	86.63	gold quality
blood	UBERON:0000178	86.24	gold quality
anterior cingulate cortex	UBERON:0009835	85.87	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	84.82	gold quality
right frontal lobe	UBERON:0002810	84.34	gold quality
amygdala	UBERON:0001876	84.20	gold quality
granulocyte	CL:0000094	83.72	gold quality
prefrontal cortex	UBERON:0000451	83.13	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.13	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	83.09	gold quality
Ammon’s horn	UBERON:0001954	81.67	gold quality
neocortex	UBERON:0001950	81.52	gold quality
spinal cord	UBERON:0002240	81.42	gold quality
medial globus pallidus	UBERON:0002477	81.36	gold quality
frontal cortex	UBERON:0001870	81.11	gold quality
cerebral cortex	UBERON:0000956	80.82	gold quality
bone marrow cell	CL:0002092	80.56	gold quality
tendon of biceps brachii	UBERON:0008188	79.46	silver quality
Brodmann (1909) area 46	UBERON:0006483	78.23	silver quality
temporal lobe	UBERON:0001871	78.19	gold quality
buccal mucosa cell	CL:0002336	77.75	silver quality
primary visual cortex	UBERON:0002436	76.50	gold quality
forebrain	UBERON:0001890	76.01	gold quality
right hemisphere of cerebellum	UBERON:0014890	75.88	gold quality
right atrium auricular region	UBERON:0006631	75.87	gold quality
ganglionic eminence	UBERON:0004023	75.66	gold quality
brain	UBERON:0000955	75.31	gold quality
globus pallidus	UBERON:0001875	75.11	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.48
E-CURD-53	no	53.07

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, TAL1

miRNA regulators (miRDB)

27 targeting NTNG2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-3960	99.41	66.11	96
HSA-MIR-5584-3P	99.23	68.79	1351
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-1286	99.09	66.23	1046
HSA-MIR-3168	99.08	67.75	1384
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-519A-2-5P	98.78	71.74	1401
HSA-MIR-520B-5P	98.78	71.74	1401
HSA-MIR-2117	98.48	67.97	1307
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-4684-5P	98.29	67.99	1650
HSA-MIR-8072	98.27	66.24	83
HSA-MIR-595	98.25	67.44	699
HSA-MIR-6511B-5P	97.98	65.64	823
HSA-MIR-6811-5P	97.98	64.96	848
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-148B-5P	97.29	66.30	992
HSA-MIR-6874-3P	97.29	66.34	975
HSA-MIR-6806-5P	96.37	68.74	587
HSA-MIR-4749-5P	92.16	62.26	179
HSA-MIR-10392-3P	88.79	61.83	122

Literature-anchored findings (GeneRIF, showing 8)

• An association between NTNG2 and schizophrenia was observed with SNPs and haplotypes that clustered in the 5’ region of the gene. (PMID:15705354)
• The data of this stusty implicate NTNG2 in the pathophysiology of schizophrenia and bipolar disorder, but do not support the hypothesis that altered mRNA expression is the mechanism by which genetic variation of NTNG2 may confer disease susceptibility. (PMID:17507910)
• Netrin-g2 is involved in the pathophysiology of epilepsy and are consistent with the hypothesis that this protein may participate in the abnormal development of synapses and in neuron migration (PMID:20382146)
• the crystal structure for a fragment comprising the LN domain and domain LE1 of netrin G2 by sulfur single-wavelength anomalous diffraction phasing and refined it to 1.8 A resolution was determined. (PMID:22041449)
• presence of Gng2 and Netrin-G2 immunoreactive elements in the insular cortex, but not in the putamen, suggests a possible common ontogeny of the claustrum and insula (PMID:22957104)
• Homozygous frameshift variant in NTNG2, encoding a synaptic cell adhesion molecule, in individuals with developmental delay, hypotonia, and autistic features. (PMID:31372774)
• Appropriate expression of NTNG2 plays an important role in neurotypical development. (PMID:31668703)
• Netrin-G2 dysfunction causes a Rett-like phenotype with areflexia. (PMID:31692205)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ntng2a	ENSDARG00000077367
danio_rerio	ntng2b	ENSDARG00000087100
mus_musculus	Ntng2	ENSMUSG00000035513
rattus_norvegicus	Ntng2	ENSRNOG00000013694

Paralogs (27): USH2A (ENSG00000042781), LAMC3 (ENSG00000050555), LAMA3 (ENSG00000053747), LAMC2 (ENSG00000058085), NTN1 (ENSG00000065320), NTN4 (ENSG00000074527), ATRN (ENSG00000088812), LAMB4 (ENSG00000091128), LAMB1 (ENSG00000091136), LAMA1 (ENSG00000101680), MEGF8 (ENSG00000105429), MEGF9 (ENSG00000106780), ATRNL1 (ENSG00000107518), LAMA4 (ENSG00000112769), LAMA5 (ENSG00000130702), LAMC1 (ENSG00000135862), NTN5 (ENSG00000142233), HSPG2 (ENSG00000142798), TMEFF2 (ENSG00000144339), NTN3 (ENSG00000162068), NTNG1 (ENSG00000162631), EGFLAM (ENSG00000164318), LAMB2 (ENSG00000172037), AGRN (ENSG00000188157), LAMA2 (ENSG00000196569), LAMB3 (ENSG00000196878), TMEFF1 (ENSG00000241697)

Protein

Protein identifiers

Netrin-G2 — Q96CW9 (reviewed: Q96CW9)

Alternative names: Laminet-2

All UniProt accessions (1): Q96CW9

UniProt curated annotations — full annotation on UniProt →

Function. Involved in controlling patterning and neuronal circuit formation at the laminar, cellular, subcellular and synaptic levels. Promotes neurite outgrowth of both axons and dendrites.

Subunit / interactions. Interacts with LRRC4.

Subcellular location. Cell membrane.

Post-translational modifications. N-glycosylated.

Disease relevance. Neurodevelopmental disorder with behavioral abnormalities, absent speech, and hypotonia (NEDBASH) [MIM:618718] An autosomal recessive disorder characterized by global developmental delay with severely impaired intellectual development, impaired motor development, axial and peripheral hypotonia, poor speech and significant behavioral abnormalities, including autism spectrum disorder, hyperactivity, mood disorders, aggression, hand and face stereotypies, sleep disturbances, anxiety, self-injurious behavior, and bruxism. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The laminin N-terminal domain mediates 1:1 binding to NGL ligand with sub-micromolar affinity. Three NGL-binding loops mediate discrimination for LRRC4C/NGL1 among other NGLs by binding specifically to its LRR repeats. This specificity drives the sorting of a mixed population of molecules into discrete cell surface subdomains.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96CW9-1	1	yes
Q96CW9-2	2

RefSeq proteins (1): NP_115925* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000742	EGF	Domain
IPR002049	LE_dom	Domain
IPR008211	Laminin_N	Domain
IPR050440	Laminin/Netrin_ECM	Family
IPR056863	LMN_ATRN_NET-like_EGF	Domain

Pfam: PF00053, PF00055, PF24973

UniProt features (81 total): strand 21, disulfide bond 19, helix 9, sequence variant 8, turn 6, glycosylation site 5, domain 4, region of interest 3, splice variant 2, signal peptide 1, chain 1, lipid moiety-binding region 1, propeptide 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3TBD	X-RAY DIFFRACTION	1.8
3ZYG	X-RAY DIFFRACTION	2.2
3ZYI	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96CW9-F1	85.03	0.57

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 507

Disulfide bonds (19): 22–39, 61–81, 69–77, 171–195, 287–296, 289–305, 307–316, 319–344, 353–362, 355–373, 376–385, 388–406, 409–421, 411–427, 429–438, 441–451, 456–469, 463–475, 477–486

Glycosylation sites (5): 122, 128, 310, 395, 422

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-163125	Post-translational modification: synthesis of GPI-anchored proteins

MSigDB gene sets: 450 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, MORF_MSH3, WHITEHURST_PACLITAXEL_SENSITIVITY, GOBP_SYNAPSE_ASSEMBLY, MORF_BRCA1, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, TGACCTY_ERR1_Q2, MORF_ESR1, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, CAGCTG_AP4_Q5, MORF_RAD51L3, GOBP_CELL_CELL_SIGNALING

GO Biological Process (10): axonogenesis (GO:0007409), regulation of neuron projection development (GO:0010975), modulation of chemical synaptic transmission (GO:0050804), postsynaptic specialization assembly (GO:0098698), synaptic membrane adhesion (GO:0099560), regulation of neuron projection arborization (GO:0150011), regulation of presynapse assembly (GO:1905606), regulation of neuron migration (GO:2001222), nervous system development (GO:0007399), cell differentiation (GO:0030154)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (8): extracellular region (GO:0005576), plasma membrane (GO:0005886), axon (GO:0030424), presynaptic active zone membrane (GO:0048787), side of membrane (GO:0098552), Schaffer collateral - CA1 synapse (GO:0098685), glutamatergic synapse (GO:0098978), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
membrane	2
synapse	2
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
neuron projection development	1
regulation of plasma membrane bounded cell projection organization	1
chemical synaptic transmission	1
regulation of trans-synaptic signaling	1
organelle assembly	1
postsynapse assembly	1
postsynaptic specialization organization	1
synapse organization	1
cell-cell adhesion	1
regulation of cell morphogenesis	1
regulation of cell projection organization	1
neuron projection arborization	1
regulation of synapse assembly	1
presynapse assembly	1
regulation of presynapse organization	1
neuron migration	1
regulation of cell migration	1
system development	1
cellular developmental process	1
binding	1
cell periphery	1
neuron projection	1
presynaptic membrane	1
presynaptic active zone	1
synaptic membrane	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

1368 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NTNG2	LRRC4C	Q9HCJ2	999
NTNG2	LRRC4	Q9HBW1	982
NTNG2	LRRC4B	Q9NT99	765
NTNG2	CDKL5	O76039	739
NTNG2	GPM6B	Q13491	685
NTNG2	GLRA2	P23416	672
NTNG2	GRPR	P30550	661
NTNG2	GLUD2	P49448	648
NTNG2	GDI1	P31150	648
NTNG2	ROBO2	Q9HCK4	596
NTNG2	MDGA1	Q8NFP4	594
NTNG2	HCCS	P53701	588
NTNG2	LXN	Q9BS40	576
NTNG2	MECP2	P51608	570
NTNG2	UNC5C	O95185	568

IntAct

11 interactions, top by confidence:

A	B	Type	Score
NTNG2	LRRC4	psi-mi:“MI:0407”(direct interaction)	0.620
LRRC4	NTNG2	psi-mi:“MI:0407”(direct interaction)	0.620
LRRC4C	NTNG2	psi-mi:“MI:0407”(direct interaction)	0.440
NTNG2	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440
NTNG2	ADRA1A	psi-mi:“MI:0915”(physical association)	0.370
NTNG2	CCR2	psi-mi:“MI:0915”(physical association)	0.370
EWSR1	NTNG2	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (8): NTNG2 (Two-hybrid), NTNG2 (Affinity Capture-MS), NTNG2 (Two-hybrid), NTNG2 (Two-hybrid), LRRC4 (Co-crystal Structure), NTNG2 (Affinity Capture-RNA), NTNG2 (Affinity Capture-MS), NTNG2 (Affinity Capture-RNA)

ESM2 similar proteins: A0A1D5PUP4, A2AFS3, M0R7X9, O70472, O75882, O95803, P01134, P26012, P52799, P52848, P69849, Q02353, Q05204, Q0VCJ8, Q12841, Q13635, Q15155, Q3UHN9, Q3ZBS2, Q58D84, Q5EA46, Q5JPE7, Q5R9Y1, Q5U4X8, Q5VV63, Q5ZJB7, Q5ZMH6, Q61115, Q62356, Q62632, Q6A051, Q6GQK9, Q6GQT9, Q6P988, Q6UXG2, Q7Z5A7, Q86TD4, Q90693, Q91WE9, Q96CW9

Diamond homologs: A0JP86, A2ASQ1, G5ECE3, O00468, O00634, O09118, O15230, O75445, O75882, O95631, P02468, P11047, P15215, P19137, P24043, P25304, P25391, P31696, P34710, P97927, Q00174, Q01635, Q13751, Q13753, Q16363, Q16787, Q18823, Q19981, Q1LVF0, Q24567, Q24568, Q27262, Q2HXW4, Q2QI47, Q5RB89, Q5VV63, Q60675, Q61001, Q61087, Q61092

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NTNG2	“up-regulates activity”	LRRC4	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

180 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	2
Uncertain significance	112
Likely benign	20
Benign	19

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
4292836	NM_032536.4(NTNG2):c.483G>A (p.Trp161Ter)	Pathogenic
690370	NM_032536.4(NTNG2):c.376dup (p.Ser126fs)	Pathogenic
1180710	NM_032536.4(NTNG2):c.422T>C (p.Phe141Ser)	Likely pathogenic
691561	NM_032536.4(NTNG2):c.599C>T (p.Ser200Leu)	Likely pathogenic

SpliceAI

6760 predictions. Top by Δscore:

Variant	Effect	Δscore
1:107162298:GATTT:G	donor_gain	1.0000
1:107162302:T:G	donor_gain	1.0000
1:107213420:G:GT	donor_gain	1.0000
1:107395327:G:GG	donor_gain	1.0000
9:132227018:GCCT:G	donor_gain	1.0000
9:132227022:G:GG	donor_gain	1.0000
9:132237419:A:G	acceptor_gain	1.0000
1:107143168:G:GA	donor_gain	0.9900
1:107162302:T:TG	donor_gain	0.9900
1:107213420:G:T	donor_gain	0.9900
1:107321431:G:GT	donor_gain	0.9900
1:107321501:T:TA	donor_gain	0.9900
1:107323213:C:CG	donor_gain	0.9900
1:107324278:ATAG:A	acceptor_gain	0.9900
1:107324279:TAGGG:T	acceptor_loss	0.9900
1:107324280:AG:A	acceptor_gain	0.9900
1:107324281:GG:G	acceptor_gain	0.9900
1:107344455:G:T	donor_gain	0.9900
1:107395322:TACCT:T	donor_gain	0.9900
1:107395323:ACCT:A	donor_gain	0.9900
1:107395324:CCT:C	donor_gain	0.9900
1:107407708:AGTA:A	donor_gain	0.9900
1:107430748:A:G	acceptor_gain	0.9900
1:107436664:GA:G	acceptor_gain	0.9900
1:107436664:GAGT:G	acceptor_gain	0.9900
1:107436800:G:GG	donor_gain	0.9900
1:107463061:A:T	donor_gain	0.9900
1:107478001:C:CA	acceptor_gain	0.9900
1:107478002:G:A	acceptor_gain	0.9900
9:132162221:G:GT	donor_gain	0.9900

AlphaMissense

3481 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:132167012:T:A	C61S	1.000
9:132167012:T:C	C61R	1.000
9:132167013:G:A	C61Y	1.000
9:132167013:G:C	C61S	1.000
9:132167013:G:T	C61F	1.000
9:132167014:T:G	C61W	1.000
9:132197993:T:A	C81S	1.000
9:132197993:T:C	C81R	1.000
9:132197994:G:C	C81S	1.000
9:132198071:T:A	W107R	1.000
9:132198071:T:C	W107R	1.000
9:132198073:G:C	W107C	1.000
9:132198073:G:T	W107C	1.000
9:132198077:A:C	S109R	1.000
9:132198079:C:A	S109R	1.000
9:132198079:C:G	S109R	1.000
9:132198086:T:A	W112R	1.000
9:132198086:T:C	W112R	1.000
9:132198088:G:C	W112C	1.000
9:132198088:G:T	W112C	1.000
9:132198189:C:A	P146H	1.000
9:132198235:G:C	W161C	1.000
9:132198235:G:T	W161C	1.000
9:132198265:C:G	C171W	1.000
9:132198335:T:A	C195S	1.000
9:132198335:T:C	C195R	1.000
9:132198336:G:A	C195Y	1.000
9:132198336:G:C	C195S	1.000
9:132198337:C:G	C195W	1.000
9:132198507:T:C	L252P	1.000

dbSNP variants (sampled 300 via entrez): RS1000055180 (9:132223597 G>A), RS1000075411 (9:132191423 C>T), RS1000173729 (9:132208225 C>T), RS1000174204 (9:132171884 C>T), RS1000174720 (9:132181094 T>C), RS1000217325 (9:132163596 G>GGAGGGA), RS1000282609 (9:132192122 G>A), RS1000283607 (9:132239214 C>T), RS1000289573 (9:132210067 G>A), RS1000297450 (9:132233940 C>T), RS1000341257 (9:132202773 C>T), RS1000401315 (9:132165957 C>A,T), RS1000492306 (9:132240282 G>T), RS1000517272 (9:132203321 C>G), RS1000532860 (9:132191150 G>T)

Disease associations

OMIM: gene MIM:618689 | disease phenotypes: MIM:616139, MIM:618718, MIM:618158, MIM:617268

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with behavioral abnormalities, absent speech, and hypotonia	Strong	Autosomal recessive
syndromic intellectual disability	Supportive	Autosomal dominant
atypical Rett syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Limited	AD

Mondo (8): developmental and epileptic encephalopathy, 27 (MONDO:0014505), neurodevelopmental disorder with behavioral abnormalities, absent speech, and hypotonia (MONDO:0032878), congenital nervous system disorder (MONDO:0002320), intellectual developmental disorder with macrocephaly, seizures, and speech delay (MONDO:0032568), neurodevelopmental disorder (MONDO:0700092), neurodevelopmental disorder with hypotonia, seizures, and absent language (MONDO:0014995), syndromic intellectual disability (MONDO:0000508), atypical Rett syndrome (MONDO:0017746)

Orphanet (1): West syndrome (Orphanet:3451)

HPO phenotypes

75 total (30 of 75 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000369	Low-set ears
HP:0000565	Esotropia
HP:0000601	Hypotelorism
HP:0000639	Nystagmus
HP:0000713	Agitation
HP:0000723	Restrictive behavior
HP:0000729	Autistic behavior
HP:0000733	Motor stereotypy
HP:0000748	Inappropriate laughter
HP:0000749	Paroxysmal bursts of laughter
HP:0000750	Delayed speech and language development
HP:0000752	Hyperactivity
HP:0000817	Reduced eye contact
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001256	Mild intellectual disability
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001288	Gait disturbance
HP:0001319	Neonatal hypotonia
HP:0001324	Muscle weakness
HP:0001332	Dystonia
HP:0001337	Tremor
HP:0001344	Absent speech
HP:0001510	Growth delay
HP:0001773	Short foot

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST000144_9	Systemic lupus erythematosus	3.000000e-06
GCST000873_7	Anorexia nervosa	6.000000e-06
GCST003469_9	Response to cognitive-behavioural therapy in anxiety disorder	2.000000e-06
GCST004904_106	Body mass index	3.000000e-08
GCST005042_1	Restless legs syndrome	3.000000e-63
GCST005917_1	Current cigarettes per day in chronic obstructive pulmonary disease	2.000000e-07
GCST006585_32	Blood protein levels	3.000000e-113
GCST008156_147	Hip circumference adjusted for BMI	9.000000e-06
GCST009391_837	Metabolite levels	8.000000e-06
GCST009996_3	HDL cholesterol levels	1.000000e-07
GCST010273_11	Gout (normal type)	5.000000e-07
GCST011354_42	Bell’s palsy	5.000000e-06
GCST012036_1	Sleep end time	1.000000e-08
GCST90012857_4	Falling risk	6.000000e-08

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0007820	cognitive behavioural therapy
EFO:0004340	body mass index
EFO:0006525	cigarettes per day measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0010399	triacylglycerol 44:1 measurement
EFO:0007805	HDL cholesterol change measurement
EFO:0008328	chronotype measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

41 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	6
Benzo(a)pyrene	decreases expression, increases methylation, affects methylation	3
Air Pollutants	affects expression, increases abundance, increases expression	2
Tretinoin	decreases expression, increases expression	2
Esketamine	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
terbufos	decreases methylation	1
trichostatin A	increases expression	1
sodium arsenite	affects methylation	1
benzo(e)pyrene	affects methylation	1
aflatoxin B2	decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
MRK 003	decreases expression	1
bisphenol S	decreases methylation	1
Fulvestrant	increases methylation	1
Acetaminophen	decreases expression	1
Atrazine	increases expression	1
Calcitriol	affects cotreatment, increases expression	1
Citrinin	decreases expression	1
Diazinon	increases methylation	1
Fonofos	decreases methylation	1
Methapyrilene	affects methylation	1
Niclosamide	increases expression	1
Ozone	increases abundance, affects expression	1
Parathion	decreases methylation	1

Clinical trials (associated diseases)

202 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice